What is the difference between numular epithelial keratitis due to adenoviral and Herpes Simplex Virus (HSV) infections?

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Distinguishing Nummular Epithelial Keratitis: Adenoviral vs HSV

The key distinction is that HSV nummular keratitis presents with excavated true epithelial defects that penetrate Bowman's layer and stain with fluorescein, while adenoviral nummular keratitis consists of non-excavated punctate epithelial lesions that represent immune-mediated subepithelial infiltrates without true ulceration. 1

Clinical Presentation Patterns

Laterality and Onset

  • HSV typically presents unilaterally with bulbar conjunctival injection and watery discharge 1
  • Adenoviral keratitis often presents sequentially bilaterally with abrupt onset and varying severity between eyes 1

Associated Conjunctival Findings

  • Preceding follicular conjunctivitis strongly favors adenovirus over HSV 1
  • The presence of bilateral involvement combined with follicular conjunctivitis makes adenoviral etiology much more likely 1

Morphological Characteristics

HSV Nummular Keratitis

  • Excavated ulcers with true epithelial defects that penetrate through the epithelium into Bowman's layer 1
  • These lesions will show positive fluorescein staining due to actual tissue loss 1
  • May be associated with dendritic or geographic epithelial patterns in acute phase 2, 3

Adenoviral Nummular Keratitis

  • Non-excavated punctate epithelial keratitis in the acute phase that evolves into subepithelial infiltrates 1
  • These represent immune-mediated inflammatory deposits rather than true ulceration 1
  • The epithelium remains intact over the infiltrates, distinguishing them from HSV lesions 1

Natural History and Timeline

HSV Course

  • Requires active antiviral treatment with topical ganciclovir 0.15% gel or trifluridine 1% solution combined with oral antivirals 1, 4
  • Without treatment, HSV epithelial keratitis may persist or progress and can lead to stromal involvement 5
  • Risk of recurrence necessitates long-term management considerations 6

Adenoviral Course

  • Self-limited disease with improvement within 5 to 14 days in most cases without specific antiviral therapy 1
  • Supportive care with preservative-free artificial tears and cold compresses is the mainstay of treatment 7
  • Subepithelial infiltrates may persist for weeks to months but gradually resolve 7

Critical Diagnostic Pitfalls

Avoiding Misdiagnosis

  • Do not confuse the non-excavated pseudodendritic pattern of varicella zoster virus with HSV's excavated dendrites or adenoviral punctate keratitis 1
  • The presence of true epithelial defects with fluorescein uptake indicates HSV rather than adenoviral disease 1

Risk of Inappropriate Steroid Use

  • Using topical corticosteroids without antiviral coverage in epithelial HSV keratitis can potentiate the infection and lead to geographic ulceration 4
  • In contrast, severe adenoviral keratitis may benefit from judicious corticosteroid use (fluorometholone, loteprednol) for symptomatic relief without the same risk of viral reactivation 7

Practical Clinical Algorithm

Step 1: Assess laterality and conjunctival findings

  • Bilateral + follicular conjunctivitis → strongly suggests adenovirus 1
  • Unilateral + minimal conjunctival involvement → consider HSV 1

Step 2: Examine lesion morphology with fluorescein

  • Excavated defects with positive staining → HSV 1
  • Non-excavated infiltrates without true ulceration → adenovirus 1

Step 3: Initiate appropriate therapy

  • HSV: Topical ganciclovir 0.15% gel 3-5 times daily PLUS oral antiviral (valacyclovir 500mg 2-3 times daily) 4
  • Adenovirus: Supportive care with preservative-free artificial tears, cold compresses, and observation 7

References

Guideline

Distinguishing Nummular Epithelial Keratitis: Adenoviral vs HSV

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

The treatment of herpes simplex virus epithelial keratitis.

Transactions of the American Ophthalmological Society, 2000

Guideline

Treatment of Herpetic Keratitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Research

["Herpetic keratitis". Various expressions require different therapeutic approaches].

Der Ophthalmologe : Zeitschrift der Deutschen Ophthalmologischen Gesellschaft, 2011

Guideline

Treatment of Viral Conjunctivitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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